The Asthma and Allergic Diseases Center of the University of Virginia is primarily concerned with investigating the etiology of asthma focusing on the foreign proteins that can cause an immune response of the type characteristic of this disease, i.e. T cells that produce IL-4 and IL-5, IgE antibodies and eosinophils. The Center combines studies on the common indoor allergens, respiratory viruses, and allergens derived from comensal organisms, which are causally related to asthma in infants, school age children and adults. Studies proposed include four main areas: i) Site-directed mutagenesis will be used to create variants of recombinant allergens (e.g. the mite allergen Der p 2) that stimulate T cells but do not bind to IgE antibodies, and could be used for immunotherapy. In parallel, the tertiary structure of Der p 2 will be determined using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. Together, these studies will provide a structural basis for dissecting the immune response to allergens. ii) Immunization with the G or F proteins of Respiratory Syncytial Virus (RSV) leads to different cytokine patterns when mice are infected with the virus. This model will be used to investigate the T cell responses that result in IL-5 production and the eosinophil infiltrate in the lungs. RSV in infancy is the most common cause of bronchiolitis. The G and F proteins will be used to investigate T cell responses in children who have been infected with RSV. iii) Population based and prospective studies on the role of allergen exposure in asthma will be used to investigate fact&s that can influence inflammation and symptoms of asthma in children. These studies will use PCR for rhinovirus and simple markers of inflammation (e.g. nasal ECP and exhaled NO) which are suitable for epidemiological studies or monitoring of acute asthma. iv) Patients with late onset or intrinsic asthma will be investigated to identify' those cases where a search for the causes of eosinophilia and/or sinusitis should be focused. A subgroup of these patients are colonized with Trichophyton, and have T cells that produce IL-5 in response to fungal proteins. Using cultures, skin tests and immunochemistry the studies will identify and characterize other potential allergens including the bacterial flora of sinuses. The D&E Project will investigate the role of cockroach and dust mite allergen control in the treatment of asthma among inner city children. All of the proposed studies are designed to identify aspects of the etiology of asthma that could lead directly to improved management.